Dietary Energy Intake, Body Composition and Resting Energy Expenditure in Prepubertal Children with Prader-Willi Syndrome before and during Growth Hormone Treatment: A Randomized Controlled Trial

Abstract

Background/Aims: Dietary management is a difficult but key aspect of care in children with Prader-Willi syndrome (PWS). We therefore investigated the effect of growth hormone (GH) treatment on reported energy intake in children with PWS, in relation with body composition, resting energy expenditure (REE) and hormone levels. Methods: In a randomized controlled GH trial including 47 children with PWS, we assessed 5-day dietary records and dual-energy X-ray absorptiometry for body composition. REE was calculated by Müller's equation, based on fat mass, fat free mass and gender. Results: Baseline energy intake of children with PWS was lower than normal daily energy requirements (p < 0.001), and decreased with age to 50% in prepubertal children. Energy intake in infants [m/f: 11/8; median (interquartile range [IQR]) age 2.7 years (1.5-3.2)] increased after 1 year of GH treatment (p = 0.008); this tended to be higher in the GH group than in the untreated group (p = 0.07). In prepubertal children [m/f: 14/14; median (IQR) age 6.8 years (5.1-8.1)], the increase in energy intake was higher in the GH group, but this was not different compared to the untreated group. REE was not different between the GH group and the untreated group. Increase in energy intake during 2 years of GH treatment was correlated with lower fat percentage standard deviation scores (p = 0.037) and higher adiponectin levels (p = 0.007). Conclusion: Our study demonstrates that parents of children with PWS are very well capable of restricting energy intake up to 50% compared to daily energy requirements for age- and sex-matched healthy children. GH treatment was associated with a slight increase in energy intake, but also improved body composition and adiponectin levels, which suggests a protective effect of GH treatment.

Growth hormone treatment in Prader-Willi syndrome patients: systematic review and meta-analysis

“…Also, the largest effect of GH treatment on adaptive functioning was reached if GH treatment was started at a younger age during infancy. 45 Muscular strength and motor development seemed to improve in treated patients according to selected articles. 5 15 16 35 37 40 44 Multilevel regression models controlled for age and baseline muscle thickness identified a statistically significant rhGH dependency in the Reus article.…”

Visceral adipose tissue increases shortly after the cessation of GH therapy in adults with Prader-Willi syndrome

“…Furthermore, as increased VAT is associated with obstructive sleep apnea syndrome [33], one of the causes of death in PWS adults, maintaining an appropriate body composition by continuation of GH therapy from childhood to adulthood is important to maintain a higher quality of life (QOL) in adult PWS patients. GH therapy improves body composition and lipid profiles both in children [34][35][36][37][38][39][40][41][42][43][44] and adults PWS patients [45][46][47][48][49][50][51][52]; therefore, continuation of GH therapy after adult height is achieved may be beneficial for maintaining body composition, which eventually reduces the risk of obesity-related complications in adults with PWS. However, GH therapy for PWS adults has not been approved globally, except for New Zealand.…”

Preclinical Testing in Translational Animal Models of Prader-Willi Syndrome: Overview and Gap Analysis

“…Clinical trials in PWS were recently reviewed 130, 131. The largest number of clinical trials in PWS have tested oxytocin or an oxytocin analog (carbetocin, intranasal FE992097), finding positive effects on both hyperphagia and behavior 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150. A trial of beloranib, a methionine aminopeptidase 2 (MetAP2) inhibitor that promotes loss of fat mass, was terminated in 2016 after adverse events involving excess blood clot formation, 151 while other MetAP2 compounds are in development 152 .…”